Session II – CTEPH

Medical and Surgical Treatment of CTEPH

In the past, treatment options for chronic thromboembolic pulmonary hypertension (CTEPH) were limited to pulmonary endarterectomy surgery or lung transplant; however, advances in medical therapies and balloon pulmonary angioplasty have increased the treatment options. Now, CTEPH is a treatable form of pulmonary hypertension, which is why it is important to refer patients to specialized centers.

After CTEPH is diagnosed, the next step is to assess upper ability, which is a technical distention. What determines operability is the location of the organized clots and the availability and capability of an endarterectomy surgeon. Another issue is whether the patient is a good surgical candidate.

The cornerstones of pulmonary endarterectomy surgery include median sternotomy, cardiopulmonary bypass, and deep hypothermia to allow for circulatory arrest and to perform a true endarterectomy. This means to remove an organized clot deeply embedded in the pulmonary artery wall, and not only an embolectomy. To perform this surgery, a bloodless field is required. However, some CTEPH patients have substantial bleeding even on full cardiopulmonary bypass, due to blood flow coming off of collateral systemic circulation. To stop that blood flow, patients need to be off bypass (ie, circulatory arrest) during certain periods. To do this circulatory arrest safely, tissue metabolism is cooled to 18 to 20 degrees Celsius (between 64 and 68 degrees Fahrenheit).

A successful endarterectomy can significantly restore pulmonary blood flow with consequent decrease in pulmonary vascular resistance, right ventricular afterload, and rapid improvement in right ventricular size and function. This hemodynamic benefit is usually sustained over the long-term, and causes improvements in functional status and exercise capacity. Surgical mortality ranges from 2% to 4%. Experienced surgeons are able to perform pulmonary endarterectomy solely at the subsegmental level. While experiencing is growing, data suggest significant improvements in pulmonary hemodynamics.

Pulmonary endarterectomy has an extensive record of success and safety, and it is the primary treatment choice for CTEPH patients. However, there are patients who are inoperable from a technical perspective or have operable disease but are not surgical candidates. For these patients, treatment options include targeted medical therapies and pulmonary angioplasty. The only FDA-approved medication for CTEPH is riociguat, a soluble guanylate cyclase stimulator shown to be effective in patients with inoperable CTEPH and in patients with residual pulmonary hypertension after surgery. In trials, it improved 6-minute walk distance and reduced pulmonary vascular resistance and other markers of right ventricular dysfunction. Other medical therapies are sildenafil and bosentan, both of which have shown preliminary evidence of efficacy in improving hemodynamics.

Balloon Pulmonary Angioplasty for CTEPH

The primary motivation for nonsurgical therapies for CTEPH is to address an unmet need for treatment in the 50% of patients who do not undergo pulmonary endarterectomy. Also, pulmonary endarterectomy fails sometimes. And finally, even after successful surgery, some patients remain restless and show no evidence of exercise limitation or right ventricular dysfunction.

Balloon pulmonary angioplasty (BPA) is an invasive percutaneous technique that follows the original idea of percutaneous coronary intervention. A balloon is inflated inside the pulmonary artery and breaks the webs. During BPA, the media of the artery is not broken, which is the main difference compared with coronary interventions. This is also why BPA is not associated with restenosis.

The initial report on BPA for CTEPH palpation in 2001 showed poor outcomes, but these have significantly improved since then. Endovascular imaging techniques, such as optical coherence tomography, allow for visualizing chronic thromboembolic lesions, particularly webs, in areas where conventional digital subtraction angiography often seems unremarkable. In practice, these advanced techniques add time to the procedure and are not routinely use. However, in our practice, we use hand injection of dilute contrast and guide the catheter, which requires a deep understanding of pulmonary vascular anatomy.

Experience is rapidly growing in Europe and Japan. Periprocedural mortality has dropped to below 2%, and there are significant improvements in functional class, exercise capacity, pulmonary vascular resistance, and cardiac index. For some reason, the cardiac index response in Japanese patients is less than in European patients, but the hemodynamic response in western countries appears less prominent than in Japan.

Lesion characteristics have become important predictors of outcome. Subtotal occlusions and tortuous lesions have the most complications. Total occlusions are currently not treated.

Complications with BPA can be classified as thoracic and nonthoracic. Thoracic complications include lung injury that manifests itself clinically with hypoxemia, hemoptysis, and lung opacities. Lung injury is currently believed to be secondary to vascular injury induced by the guiding catheter, balloon, or wire. Vascular injury can range from perforation to dissection. Other thoracic complications include bleeding, pulmonary infections, and potentially reperfusion, although the latter has been questioned.

Nonthoracic BPA complications include arrhythmia, renal failure, allergic reactions, radiation injury, and axis site complications. There are several ways to manage these complications including high flow oxygen supplementation, wedging of the affected artery with balloon or guiding catheter, injection of gelatin, coiling, stenting, endotracheal intubation, positive-pressure ventilation, and extracorporeal membrane oxygenation.

The role of BPA is evolving. Registry data will be important in providing outcomes data on BPA, and an international BPA registry is getting started. It may be that BPA will become the therapeutic standard; however, pulmonary endarterectomy remains the treatment of choice. It is recommended that a CTEPH center needs to provide pulmonary endarterectomy surgery, balloon pulmonary angioplasty, medical therapy, and have extracorporeal membrane oxygenation capabilities.

Key Points

• After CTEPH is diagnosed, the next step is to assess upper ability, which is a technical distention. What determines operability is the location of the organized clots and the availability of an endarterectomy surgeon. Another issue is whether the patient is a good surgical candidate. These decision are best made at an expert CTEPH center.
• The cornerstones of pulmonary endarterectomy surgery include median sternotomy, cardiopulmonary bypass, and deep hypothermia to allow for circulatory arrest and to perform a true endarterectomy.
• The only FDA-approved medication for CTEPH is riociguat, a soluble guanylate cyclase stimulator shown to be effective in patients with inoperable CTEPH and in patients with residual pulmonary hypertension after surgery.
• Balloon pulmonary angioplasty has emerged as a treatment option for inoperable CTEPH. Lesion characteristics have become important predictors of outcome with balloon pulmonary angioplasty: Subtotal occlusions and tortuous lesions have the most complications; total occlusions are currently not treated.

Session II – CTEPH References

Medical and Surgical Treatment of CTEPH Related References

1. Corsico AG, D’Armini AM, Cerveri I, et al. Long-term outcome after pulmonary endarterectomy. Am J Respir Crit Care Med. 2008;178(4):419-24.
D’Armini AM, Cattadori B, Monterosso C, et al. Pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension: hemodynamic characteristics and changes. Eur J Cardiothorac Surg. 2000;18(6):696-701.
2. Galie N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015;46(4):903-75.
3. Ghofrani HA, D’Armini AM, Grimminger F, et al; CHEST-1 Study Group. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med. 2013;369(4):319-29.
4. Ghofrani HA, Simonneau G, D’Armini AM, et al; MERIT study investigators. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study. Lancet Respir Med. 2017;5(10):785-794.
5. Jaïs X, D’Armini AM, Jansa P, et al. Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension: BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial. J Am Coll Cardiol. 2008;52(25):2127-34.
6. Mayer E, Dahm M, Hake U, et al. Mid-term results of pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension. Ann Thorac Surg. 1996;61(6):1788-92.

Balloon Pulmonary Angioplasty for CTEPH Related References

1. Galie N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015;46(4):903-75.
2. Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016;37(1):67-119.
3. Lang IM, Madani M. Update on chronic thromboembolic pulmonary hypertension. Circulation. 2014;130(6):508-18.
4. Olsson KM, Wiedenroth CB, Kamp JC, et al. Balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension: the initial German experience. Eur Respir J. 2017;49(6).
5. Pepke-Zaba J, Delcroix M, Lang I, et al. Chronic thromboembolic pulmonary hypertension (CTEPH): results from an international prospective registry. Circulation. 2011;124(18):1973-81.